[JBC] TGR: Two Isoforms Are Better than One

Immunoblot analysis of mouse testis lysate (lane 2) reveals the presence of two forms of TGR.

Thioredoxin/glutathione reductase is an important selenoenzyme in mammalian cells and is particularly abundant in testes. An interesting element of TGR and other mammalian thioredoxin reductases is that they generally lack AUG start codons for translation initiation, a feature common in viruses and bacteria but extremely rare in eukaryotes. In this study, the researchers combined immunoblot assays and proteomic techniques to identify a CUG codon as the start point of translation in mouse TGR. Mutational analysis revealed that the use of this codon occurs in an internal ribosome entry site-independent mechanism that likely relies on an upstream Kozak consensus sequence. As a result, the CUG start codon is quite inefficient and allows downstream translation from an internal AUG codon, thus generating two isoforms of the TGR protein. Because nonmammalian TGRs retain standard AUG start codons, the researchers believe the use of alternative start codons in mammals evolved to provide inefficient translation initiation so two forms of TGR could be produced from a single mRNA species.